This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

Metagenomic biomarker discovery and explanation

Differences in Gut Microbiota in Patients With vs Without Inflammatory Bowel Diseases: A Systematic Review.

Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.

/pdf/noncoding-rnas-in-gastric-cancer-implications-for-drug-3w5e7wjv27.pdf

Noncoding RNAs in gastric cancer: implications for drug resistance

Whole-Virome Analysis Sheds Light on Viral Dark Matter in Inflammatory Bowel Disease

Chronic stress is known to promote inflammatory bowel disease (IBD), but the underlying mechanism remains largely unresolved. Here, we found chronic stress to sensitize mice to dextran sulfate sodium (DSS)-induced colitis; to increase the infiltration of B cells, neutrophils, and proinflammatory ly6Chi macrophages in colonic lamina propria; and to present with decreased thymus and mesenteric lymph node (MLN) coefficients. Circulating total white blood cells were significantly increased after stress, and the proportion of MLN-associated immune cells were largely changed. Results showed a marked activation of IL-6/STAT3 signaling by stress. The detrimental action of stress was not terminated in IL-6−/− mice. Interestingly, the composition of gut microbiota was dramatically changed after stress, with expansion of inflammation-promoting bacteria. Furthermore, results showed stress-induced deficient expression of mucin-2 and lysozyme, which may contribute to the disorder of gut microbiota. Of note is that, in the case of cohousing, the stress-induced immune reaction and decreased body weight were abrogated, and transferred gut microbiota from stressed mice to control mice was sufficient to facilitate DSS-induced colitis. The important role of gut microbiota was further reinforced by broad-spectrum antibiotic treatment. Taken together, our results reveal that chronic stress disturbs gut microbiota, triggering immune system response and facilitating DSS-induced colitis.

/pdf/chronic-stress-promotes-colitis-by-disturbing-the-gut-k8hrpwf3mz.pdf

Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response

MiR-181a suppresses autophagy and sensitizes gastric cancer cells to cisplatin.

The factors driving the composition of gut microbiota are still only partly understood but appear to include environmental, cultural, and genetic factors. In order to obtain more insight into the relative importance of these factors, we analyzed the microbiome composition in subjects of Tibetan or Han descent living at different altitudes. DNA was isolated from stool samples. Using polymerase chain reaction methodology, the 16S rRNA V1–V3 regions were amplified and the sequence information was analyzed by principal coordinates analysis and Lefse analyses. Contrasting the Tibetan and Han populations both living at the 3600 m altitude, we found that the Tibetan microbiome is characterized by a relative abundance of Prevotella whereas the Han stool was enriched in Bacteroides. Comparing the microbiome of Han stool obtained from populations living at different altitudes revealed a more energy efficient flora in samples from those living at higher altitude relative to their lower-altitude counterparts. Comparison of the stool microbiome of Tibetan herders living at 4800 m to rural Tibetans living at 3600 m altitude shows that the former have a flora enriched in butyrate-producing bacteria, possibly in response to the harsher environment that these herders face. Thus, the study shows that both altitude and genetic/cultural background have a significant influence on microbiome composition, and it represents the first attempt to compare stool microbiota of Tibetan and Han populations in relation to altitude.

/pdf/comparative-analysis-of-gut-microbiota-of-native-tibetan-and-3fdydqqd67.pdf

Comparative Analysis of Gut Microbiota of Native Tibetan and Han Populations Living at Different Altitudes.

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease.

// Youlian Zhou 1 , Hanchang He 2 , Haoming Xu 1 , Yingfei Li 1 , Zhiming Li 1 , Yanlei Du 1 , Jie He 1 , Yongjian Zhou 1 , Hong Wang 1 , Yuqiang Nie 1 1 Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, 510180, China 2 The First People’s Foshan Hospital, Chancheng District, Foshan, 528000, Guangdong, China Correspondence to: Yuqiang Nie, email: nieyq@medmail.com.cn Keywords: colorectal cancer, fusobacterium spp., enterococcus faecalis, enterotoxigenic bacteroidesfragilis, enteropathogenic escherichia coli Received: June 29, 2016      Accepted: October 28, 2016      Published: November 04, 2016 ABSTRACT To quantify Fusobacterium spp., Enterococcus faecalis (E.faecalis), Enterotoxigenic Bacteroides fragilis (ETBF), and Enteropathogenic Escherichia coli in colorectal cancer (CRC) patients and their possible association with CRC clinicopathogical features, we collected the resected tumors and adjacent normal tissues (N) from 97 CRC patients. 48 age- and sex-matched healthy controls (HC) were also recruited. Real-time PCR was used for bacterial quantification. The median abundance of Fusobacterium spp .( p < 0.001, vs. N ; p < 0.01,vs. HC), E.faecalis ( p < 0.05, vs. N ; p < 0.01, vs. HC) and ETBF ( p < 0.001, vs. N; p < 0.05,vs. HC) in tumor tissues was significantly higher than that detected in normal tissue and HC. E.faecalis was detected in 95.88% of tumors and 93.81% of adjacent tissues. Fusobacterium spp. was detected in 72.16% of tumors and 67.01% of adjacent tissues. The combined E.faecalis and Fusobacterium spp. were detected in 70.10% of tumors and 36.08% of adjacent normal tissues. All four bacteria were detected in 33.72% and 22.09% of paired tumor and adjacent normal tissues, respectively. E.faecalis and Fusobacterium spp. are enriched in both tumor and adjacent tissue of CRC patients when compared to HC, suggesting that it is possible to be previously undetected changes in the pathohistologically normal colon tissue in the proximity of the tumor.

https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=13094&path%5B%5D=41502

Association of oncogenic bacteria with colorectal cancer in South China

Acquired immune deficiency syndrome (AIDS), caused by infection with human immunodeficiency virus (HIV), is associated with gastrointestinal disease, systemic immune activation and changes in the gut microbiota. Here, we aim to investigate the gut microbiota patterns of HIV-infected individuals and HIV-uninfected individuals in populations from South China. We enrolled 33 patients with HIV (14 participants treated with highly active antiretroviral therapy [HAART] for more than 3 months; the remaining 19 individuals had not received treatment) and 35 healthy controls (HC) for a cross-sectional comparison of gut microbiota using stool samples. Gut microbial communities were profiled by sequencing the bacterial 16S rRNA genes. Dysbiosis was more common among patients with AIDS compared with healthy individuals. Dysbiosis was characterized by decreased α-diversity, low mean counts of Bacteroidetes, Faecalibacterium, Prevotella, Bacteroides vulgatus, Dialister and Roseburia inulnivorans, and high mean counts of Proteobacteria, Enterococcus, Streptococcus, Lactobacillus, Lachnociostridium, Ruminococcus gnavus and Streptococcus vestibularis. Increased abundance of Bacilli was observed in homosexual patients. Proteobacteria were higher among heterosexual patients with HIV infections. Tenericutes were higher among patients with history of intravenous drug abuse. Restoration of gut microbiota diversity and a significant increase in abundance of Faecalibacterium, Blautia and Bacteroides were found in patients receiving HAART compared to those who did not receive. HIV infection-associated dysbiosis is characterized by decreased levels of α-diversity and Bacteroidetes, increased levels of Proteobacteria and the alterations of gut microbiota correlate with the route of HIV transmission. The imbalanced faecal microbiota of HIV infection is partially restored after therapy.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.13508

Hong Wang

Papers

MiR-181a suppresses autophagy and sensitizes gastric cancer cells to cisplatin.

Comparative Analysis of Gut Microbiota of Native Tibetan and Han Populations Living at Different Altitudes.

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease.

Association of oncogenic bacteria with colorectal cancer in South China

Alterations in the gut microbiota of patients with acquired immune deficiency syndrome.